The purpose of these experiments is to increase our general understanding of the cellular mechanisms of the immune response. The general phenomenon of lymphocyte (T cell - B cell) interactions will be explored. Whether or not organisms respond to a particular antigenic stimulus, by producing humoral antibodies, is genetically controlled by immune response (Ir) genes. One class of these genes is linked to the major histocompatibility locus, H-2, in mice. The human analogue is the HL-A histocompatibility system. The mechanism of non-response by mice to some antigens is unknown. It is also unknown whether T cells and B cells can only interact if they are of the same H-2 type. We propose experiments to help answer these two questions. The system we plan to use is that of allophenic (tetraparental) mice in which T cells and B cells of two different histocompatibility types can be combined. The two populations of cells are also chosen so that responder and non-responder cells (to particular antigens) are combined. The basic understanding of T cell - B cell interactions and the control of such interactions by immune response genes is vital for a complete understanding of the mechanism of the immune response. This in turn is vital for the understanding of allergy, cancer, and rejection of organ transplants. BIBLIOGRAPHIC REFERENCES: Warner, C. and Versteegh, L. R., "Multiple Forms of RNA Polymerase in Preimplantation Mouse Embryos," Proceedings of the Third International Conference on Isozymes, III, 45 (1975). Versteegh, L.R. and Warner, C., "A Comparative Study of Mouse Liver and Mouse Blastocyst DNA-dependent RNA Polymerases," Arch. Biochem. Biophys., 168, 133 (1975).